In ten NIH-supported core projects conducted by the nine co- investigators of this proposal, the enhanced analytical sensitivity, high- throughput, and precise molecular mass determination of Liquid Chromatography/Tandem Mass Spectroscopy (LC/MS-MS) would provide essential capabilities to enhance these projects, given the common need for rapid and precise quantitation from biological samples of pharmacologica1 agents, their in vivo metabolites, or fragments of proteins and peptides. We seek to acquire state-of-the-art LC/MS-MS instrumentation to support and enhance these research programs, as well as open new research avenues in basic molecular biochemistry. This instrument would represent the only research-grade LC/MS-MS available in a wide geographical area. It will be integrated into a central core facility, which would provide these services to a concentrated population of researchers engaged in basic and applied biomedical research who have extensive, demonstrable need for LC/MS-MS capabilities. The availability of this modem instrumentation, which would provide high- throughput analytical capabilities and computer-controlled data acquisition/management, would not only enhance productivity by eliminating more tedious, labor intensive, and less sensitive Liquid Chromatography (LC) -based assays, but would also make possible experimental approaches that are not feasible with any existing instrument. Furthermore, acquisition of this instrument would have a direct impact on human well-being, given the role of some of these investigators in ongoing clinical trials of the NIH, in the area of pharmacotherapy for MDS and drug abuse. Therefore, these existing and potential research capabilities will enhance greatly a substantial number of existing, pending, and planned NIH-supported projects of broad scope and impact.